article · Current Eye Research
This laboratory study investigates the pharmacological effects and mechanisms of L-cysteine, a precursor for hydrogen sulfide production, on isolated pig iris tissue. Researchers pre-contracted porcine iris muscle strips with carbachol and measured changes in tension following the addition of L-cysteine. L-cysteine produced concentration-dependent muscle relaxation, reaching up to 43 percent inhibition. This relaxant response was significantly strengthened by the cyclooxygenase inhibitor flurbiprofen and closely mimicked by direct hydrogen sulfide donor compounds. Further tests demonstrated that blocking the enzyme cystathionine beta-synthase or inhibiting ATP-sensitive potassium channels reduced L-cysteine-induced relaxation. Blocking cystathionine gamma-lyase also reduced relaxation at high L-cysteine concentrations. The findings show that L-cysteine relaxes isolated porcine iris smooth muscle through local hydrogen sulfide generation involving both enzymes, with functional contributions from prostanoid pathways and potassium channels.
Understanding how natural amino acids and biological gases influence eye muscles helps clarify ocular smooth muscle regulation. By identifying that hydrogen sulfide acts as a relaxing mediator in the mammalian iris, this work details specific enzymatic and channel pathways that control eye muscle tone, contributing to foundational knowledge of ocular pharmacology.
The abstract does not indicate an application pathway, as it represents very early-stage basic pharmacological research conducted on isolated animal tissue strips.
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PURPOSE: To investigate the direct pharmacological actions of L-cysteine, a substrate for the production of H(2)S, on isolated porcine irides in the presence of tone induced by muscarinic receptor stimulation. Furthermore, we examined the underlying mechanism of action of L-cysteine in this smooth muscle. METHODS: Isolated porcine iris muscle strips were set up in organ baths containing oxygenated Krebs buffer solution at 37 degrees C. Longitudinal isometric tension was recorded via a grass FT03 Force-Displacement Transducer and analyzed using the PolyView computer software. The relaxant action of L-cysteine on carbachol-induced tone was studied in the absence and presence of inhibitors of enzymes of the biosynthetic pathways for H(2)S, and prostanoids. In addition, we also examined the effect of ATP-sensitive K(+) (K(ATP)) channel antagonist, glibenclamide on relaxations induced by L-cysteine. RESULTS: L-cysteine (30 nM-1 mM) evoked concentration-dependent relaxations of carbachol-induced tone in isolated porcine irides, reaching a maximum inhibition of 43% at 1 mM. This response was enhanced significantly (P < 0.001) in the presence of the COX inhibitor, flurbiprofen (3 microM). Additionally,in the presence of flurbiprofen, the H(2)S donors, NaHS and Na(2)S, mimicked the relaxations produced by L-cysteine, yielding IC(50) values of 5.8 microM and 180 microM, respectively. Both the inhibitor of cystathionine beta-synthase, AOA (30 microM) and the K(ATP) channel antagonist, glibenclamide (100 microM) caused significant (P < 0.001) rightward shifts in the concentration-response curves to L-cysteine and attenuated the maximum inhibitory response. Conversely, the inhibitor of cystathionine gamma-lyase, PAG (1 mM) blocked only relaxations caused by high concentrations of L-cysteine (> 100 microM). CONCLUSIONS: The inhibitory action of L-cysteine in isolated porcine irides is dependent on the endogenous production of H(2)S by cystathionine gamma-lyase and cystathionine beta-synthase. Furthermore, prostanoids and K(ATP) channels are involved in the inhibitory action of L-cysteine in this tissue.
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DOI: 10.3109/02713680903576716
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